NM_012280.4:c.-29G>A

Variant names:

• chrX-48478019-G-A
• rs782600419
• NM_012280.4:c.-29G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_012280.4(FTSJ1):​c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,209,618 control chromosomes in the GnomAD database, including 1 homozygotes. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000097 (1 hom. 34 hem.)
• Consequence: FTSJ1 NM_012280.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.170
• Publications: 0 publications found

Genes affected

FTSJ1 (HGNC:13254): (FtsJ RNA 2'-O-methyltransferase 1) This gene encodes a member of the methyltransferase superfamily. The encoded protein localizes to the nucleolus, binds to S-adenosylmethionine, and may be involved in the processing and modification of ribosomal RNA. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

FTSJ1 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 9

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant X-48478019-G-A is Benign according to our data. Variant chrX-48478019-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3771129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012280.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	NM_012280.4	MANE Select	c.-29G>A		5_prime_UTR	Exon 2 of 13	NP_036412.1	A0A024QYX5
	FTSJ1	NM_001441197.1		c.-29G>A		5_prime_UTR	Exon 2 of 11	NP_001428126.1
	FTSJ1	NM_001441198.1		c.-29G>A		5_prime_UTR	Exon 3 of 12	NP_001428127.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	ENST00000348411.3	TSL:1 MANE Select	c.-29G>A		5_prime_UTR	Exon 2 of 13	ENSP00000326948.2	Q9UET6-1
	FTSJ1	ENST00000898808.1		c.-29G>A		5_prime_UTR	Exon 3 of 14	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.-29G>A		5_prime_UTR	Exon 2 of 13	ENSP00000568871.1

Frequencies

GnomAD3 genomes AF: 0.0000893 AC: 10 AN: 111978 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000949

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000940

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 21 AN: 182279 AF XY: 0.0000748

Gnomad AFR exome AF: 0.0000765

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000975 AC: 107 AN: 1097640 Hom.: 1 Cov.: 30 AF XY: 0.0000936 AC XY: 34 AN XY: 363056

African (AFR) AF: 0.0000379 AC: 1 AN: 26394

American (AMR) AF: 0.000313 AC: 11 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19375

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30197

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54083

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40407

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.000107 AC: 90 AN: 841805

Other (OTH) AF: 0.0000434 AC: 2 AN: 46072

GnomAD4 genome AF: 0.0000893 AC: 10 AN: 111978 Hom.: 0 Cov.: 23 AF XY: 0.0000585 AC XY: 2 AN XY: 34176

African (AFR) AF: 0.000130 AC: 4 AN: 30754

American (AMR) AF: 0.0000949 AC: 1 AN: 10533

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3587

South Asian (SAS) AF: 0.00 AC: 0 AN: 2745

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6107

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000940 AC: 5 AN: 53188

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		-0.17
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782600419; hg19: chrX-48336407;